EARLY SENSORY PATHWAY DYSFUNCTION IN A DOWN SYNDROME RAT MODEL

Auditory processing deficits in Down syndrome (DS) critically impede language acquisition and cognitive development. While these deficits are partially conductive in origin, they are also thought to encompass sensorineural aspects. Early studies reported shortened latencies of auditory brainstem responses, however more recent work in humans and DS mouse models has found no consistent effects. Cortical auditory evoked potentials, on the other hand, are consistently delayed in DS. The medial geniculate body (MGB) constitutes a critical relay between brainstem and cortex and is crucial for integrating and modulating auditory signals. Here, we investigated whether auditory deficits in DS emerge already at the thalamic stage of processing using a rat model of DS. The rat DS model carries a duplication of a segment of rat chromosome 20 and recapitulates multiple neural and behavioral alterations observed in human DS. We performed extracellular recordings with 384-channel Neuropixels probes from the MGB of anesthetized DS and wild-type (WT) rats aged 4-7 months and characterized neuronal responses to narrow-band auditory stimulation. DS rat MGB unit responses exhibited reduced sensitivity and prolonged latencies to auditory stimuli across the frequency range investigated (500 Hz - 22 kHz). Applying information theory and support vector machine frameworks, we found the DS MGB populations carried less stimulus-related information. Together, these findings demonstrate that DS related impairments in signal encoding emerge already in the thalamus, establishing early sensory processing as a measurable framework for understanding DS neural deficits and for evaluating therapeutic strategies.